Although writers have described episodes of depression since antiquity, only recently have we recognized that the depressive disorders are among the most common and disabling medical conditions throughout the world.

The term depression describes a group of conditions characterized by significant and sustained periods of low mood, associated with a syndrome, or group, of accompanying characteristics and symptoms. Although writers have described episodes of depression since antiquity, only recently have we recognized that the depressive disorders are among the most common and disabling medical conditions throughout the world. Approximately 5 percent to 7 percent of the adult population of the United States will suffer from a form of depression during any year, and the lifetime risk may exceed 15 percent. Depressions are outside the bounds of normal fluctuations of mood; they are not simply extreme periods of sadness. The closest parallel to depression in daily life is the grief experienced after the death of a loved one. In addition to the “blue” or melancholy mood, a depressive episode is defined by disturbances of at least four other psychological and physical processes, such as appetite, sleep, energy, concentration, interest, and the ability to experience pleasure. Some forms of depression are so severe that the person may become completely incapacitated, hallucinate (for example, “hear voices”), or develop delusions (unshakable but absolutely untrue beliefs, such as the conviction that he or she has cancer or is being punished by God for past sins). People with such severe depressions clearly appear unwell—they may be slow in action and thought, or restless, nervously pacing, and picking at their skin or nails. Their posture is often slumped, and their faces marked by down-turned mouth, lowered gaze, and furrowed brow. On the other hand, milder forms of depression can involve such subtle changes in appearance and behavior that a suffering individual’s loved ones or employer may not be sure anything is wrong. Even so, these milder forms of depression can take a toll on work performance, home life, and overall well-being. Some depressed people are not even aware of their low mood. Instead, they may complain of “burnout” or stress, feeling perpetually tired, or inexplicably losing their enthusiasm. Such “masked depression” often goes untreated, or a person will receive treatment only for a symptom, such as insomnia or vague pain complaints (back pain, chronic pain), rather than for the overall disorder. Pessimism is a hallmark of depression; it can make people seem indecisive, irritable, or less confident in their abilities. The depressed person may appear to be preoccupied with past failures, heartbreaks, or grievances. Underperformance and absenteeism negatively affect the workplace. Performance in social roles as a parent, spouse, and friend similarly suffers. Chores go undone, formerly enjoyable hobbies and social activities diminish, and even attention to grooming may decrease. Recent surveys have shown that depression has an effect on the quality of daily life comparable to heart disease and greater than most other common medical illnesses. Thoughts of death are common in depression, and most depressed people experience at least passive thoughts of suicide—that is, thinking about it without taking action. Across a lifetime, more than 20 percent of depressed people will make a suicidal attempt, such as cutting their wrists or taking a medication overdose, and about 6 percent ultimately will die by suicide. In fact, approximately three fourths of people who commit suicide have a depressive disorder. Depressions also worsen the outcome of common illnesses such as diabetes, stroke (ischemic, hemorrhagic ), and heart disease. Beyond the increased risk of early death, depression costs U.S. society tens of billions of dollars because of absenteeism from work and prolonged periods of disability. The Forms of Depression There are two general forms of depressive disorder, as well as a number of subforms and related conditions. The most common form, called major depressive disorder, is diagnosed when the mood disturbance and symptom profile has persisted almost every day for at least two weeks. Usually, a depressive episode is characterized by insomnia and decreased appetite. We use the term atypical depression when a person is oversleeping or shows an increased appetite. Sometimes a person’s low mood appears to be related to some recent setback or adversity. If such an individual’s mood disturbance or symptoms are mild, fluctuating, or short-lived, we might call the episode an adjustment disorder with depressed mood. However, once the person’s mood or behavior has been changed for long enough to meet the definition of major depressive disorder, that is the diagnosis no matter what has been happening in his or her life. About 75 percent of major depressive disorders are recurrent, meaning that the person will suffer two or more episodes in his or her lifetime. The average number of episodes, studies say, ranges between four and eight. They may be widely spaced, or, in what is called a seasonal pattern, they may occur at the same time each year, almost like clockwork. At least 10 percent of people with depression will also experience episodes of mania, an abnormal state of elation and behavioral excitement. In this case, the person is probably suffering from bipolar disorder. It is difficult to tell the difference between depressive episodes associated with bipolar disorder and major depressive disorder, so the key to diagnosis is recognition of the prior manic (or milder, hypomanic) episodes. Bipolar depressive episodes also tend to last longer, have a greater likelihood of psychotic features, and convey a greater risk of suicide. The second basic form of depression is called dysthymia or dysthymic disorder, which represents a longer-lasting but symptomatically milder disorder. Dysthymia, which accounts for about one quarter of depressive disorders, is defined by at least two years of continued mood disturbance, along with at least two associated symptoms. Despite involving fewer symptoms, dysthymia causes as much impairment in quality of life as major depressive disorder. Long-term studies suggest that without treatment, the average episode of dysthymia may last for ten or more years. Frequently beginning in childhood or adolescence, dysthymia may color a person’s personality development and negatively affect his or her vocational and interpersonal development for decades. Moreover, people with dysthymia are at great risk of developing superimposed episodes of more severe, major depression (also called double depression). Factors and Causes Depression is commonly associated with a number of other psychiatric conditions, including alcoholism, nicotine dependence, and other forms of addiction; various anxiety disorders; and personality disorders. People with schizophrenia often experience significant periods of low mood and suicidal thinking. Depression also frequently accompanies the early stages of Alzheimer’s disease. Many medical conditions (such as hypothyroidism) and numerous medications (including birth control pills) can cause depressive syndromes. These clinical complexities underscore the importance of receiving a careful diagnostic evaluation before a person assumes that the problem is a major depressive disorder. Our understanding of the causes of depression has shifted over the centuries. At the broadest level, we now view depression as a state of disturbed brain responses to internal and external signals of stress. Again, we can relate this perspective to how we view grief, as well as to the experimental condition known as learned helplessness (a state of behavioral and neurochemical “exhaustion” observed in animals after exposure to chronic or recurrent, inescapable stress). Studies of important neurochemicals, such as norepinephrine, serotonin, and corticotrophin-releasing hormone, show disturbed brain function in depression, as do alterations in brain wave activity during sleep. More recently, studies using brain imaging techniques have observed changes in cerebral blood flow and metabolism. The risk of depression is increased by genetic factors. Children of a depressed father or mother will have at least twice the lifetime risk of depression even if they are raised in another home. But heredity is not always a controlling factor, the identical twin of a person with depression has only about a 60 percent to 70 percent lifetime risk. Other factors include a history of abuse or trauma early in life, alcoholism or substance abuse, and (as noted before) many chronic medical illnesses and some medications. People with other psychiatric disorders, particularly the anxiety disorders, are also at greater risk for episodes of depression. Women are at greater risk than men for major depressive disorder and dysthymia. Most often, the first lifetime episode of depression follows a significant loss, such as a romantic rejection or a failure at work or school. Having strong, supportive personal relationships may help buffer people against the effects of such adversity. Conversely, having loved ones who are harshly critical may have the opposite effect. Psychological factors such as negative attitudes and the tendency to worry or feel overly responsible can also amplify the impact of stress. Psychological and social risk factors may become less important causal factors in more severe, recurrent, or psychotic depressive episodes, but depression is rarely a strictly medical disease. Many of the changes in the brain during an episode of depression resemble the effects of severe, prolonged stress. These changes can include a reduction in the activity of brain systems involving serotonin neurons, poor regulation of brain systems involving norepinephrine neurons, and increased amounts of cortisol and related stressresponsive hormones. It is likely that such other brain chemicals as dopamine, acetylcholine, and several neurokinins are also involved. The balance between these chemical systems helps control basic biological processes like sleep, appetite, energy, and sex drive. Together they permit expression of normal moods and emotions. Low brain serotonin activity in particular has been associated with a greater risk of completed suicide and more violent or impulsive suicide attempts. Sustained stress (and, among various animals, a loss of social rank) has been shown to lower brain serotonin levels. It also appears that some people have reduced serotonin function naturally, perhaps as an inherited characteristic. This may have important therapeutic implications. Changes in brain wave electrical patterns during sleep have been linked to depression for nearly 40 years. These alterations include a reduction of deep sleep, increased wakefulness, and increased amounts of rapid eye movement (dream) sleep, especially early in the night. Other changes in the biology of sleep during depression include a relatively increased body temperature, higher nighttime cortisol levels, and blunted release of growth hormone. Severe depression has also been associated with shifts in cerebral blood flow and changes in the rate of brain glucose metabolism. Blood flow to the higher cortical areas can be diminished (especially in the prefrontal cortex), whereas we see increased blood flow and metabolism in central brain structures that process more basic emotional and behavioral responses. There is evidence that trauma early in life may have persistent, far-reaching effects on brain stress response systems. Further, disturbances in the patterns of sleep brain waves and stress hormones secretion tend to become more marked as people have multiple episodes of depression. Severe, recurrent, and psychotic depressions may actually cause a reduction in the volume of brain tissue in some regions. Treating Depression Episodes of major depression range in duration from a few weeks to years. Without treatment, most uncomplicated depressions will remit spontaneously within one year. For the majority of people, therefore, the benefits of effective treatment are reduced time of illness and diminished suffering. Because of the high likelihood of subsequent recurrent episodes and the unpredictability of suicidal behavior, as well as depression’s apparent cumulative harm to social and brain functioning, the long-term benefits of prompt and rigorous treatment are extensive. One of the challenges of depression, however, is that it lowers a person’s will to change things for the better, and often family members and friends must push a depressed person to find help. The treatment of choice for depression depends on several factors. When a person has no history of mania and no psychotic symptoms, the initial options usually include counseling or psychotherapy and various forms of antidepressant medications. Bipolar and psychotic forms of depression should not be treated with psychotherapy alone. Bipolar depressions usually require treatment with a mood stabilizer (that is, lithium or valproate), either alone or in combination with antidepressant therapy. Psychotic depressions typically warrant treatment with a combination of antidepressant and antipsychotic medications. Electroconvulsive therapy (ECT), sometimes called shock treatment, is usually reserved for more severe depressions that have not responded to medication therapy. All modern forms of psychotherapy for depression aim to help the person clarify and solve stressful problems, if possible; learn ways to cope more effectively with depressive symptoms; and increase involvement in healthy, nondepressive activities. Modes of therapy differ in how they emphasize the interpersonal, cognitive, or behavioral aspects of depression, but all are intended to help people feel better after a few months of regular sessions. While cognitive therapy might emphasize the decrease in dysfunctional thoughts or distorted information processing, interpersonal therapy might seek to improve social adjustment by dealing with interpersonal disputes or social role traditions. Therapy is usually provided as weekly individual sessions, but forms for couples and groups are also available. Most studies of outpatients with major depressive disorder have found that the newer psychotherapies are as effective as standard antidepressant medications, although the effects of psychotherapy are sometimes slower. If psychotherapy has not resulted in significant improvement within three to four months, other treatments should be considered. Antidepressant medications are the preferred treatment for more severe depressions or when psychotherapy has not been helpful. Antidepressants are prescribed by both psychiatrists and primary care physicians. There are many different types of antidepressant medication—varying in effects, how safe they are in cases of overdose, and cost. These medications appear to help restore or rebalance the way brain systems involving serotonin or norepinephrine cells transmit their signals. That effect may in turn cause changes in the genes involved in regulating stress responses and other vital functions. Antidepressant medications do not dramatically or rapidly lift people’s spirits. Rather, they usually work more slowly, typically over four to eight weeks, even though some symptomatic improvement is often noted within seven to ten days. When an antidepressant is effective, a person must usually take it for at least six to nine months to protect against relapse. It is often recommended that people who have suffered repeated episodes of depression remain on antidepressants indefinitely. The major classes of antidepressants are so different from each other that the failure of one type does not mean that another type will not be effective. The medications come in many groupings: * Selective serotonin reuptake inhibitors (SSRIs): fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro). These are the most widely prescribed antidepressants today. As their name implies SSRIs have a much stronger effect on serotonin than on norepinephrine and other brain chemicals. * Newer antidepressants: venlafaxine XR (Effexor), bupropion (Wellbutrin), nefazodone (Serzone), and mirtazapine (Remeron). With the exception of Effexor, these medications do not have strong effects on serotonin reuptake. * Tricyclic antidepressants (TCAs): amitriptyline, imipramine, doxepin, and nortriptyline, among others. When compared with the newer medications, TCAs tend to have more side effects and are more dangerous in over-dose. Nevertheless, they can still be effective if other medications have failed. * Monoamine oxidase inhibitors (MAOIs): phenelzine (Nardil), tranylcypromine (Parnate). MAOIs have the same comparative drawbacks and potential as TCAs. They require following a diet that is low in the amino acid tyramine (certain cheeses contain this amino acid) in order to prevent sudden high blood pressure reactions. Antidepressant medications and psychotherapy are commonly used together. For people with more severe, chronic, or recurrent forms of depression, this combination may improve the chances that the problem will respond or remit completely. Response rates for particular forms of psychotherapy or antidepressant medications usually average about 50 percent to 60 percent within 6 to 12 weeks. Approximately eight out of ten people who begin treatment for depression will respond to the first, second, third, or fourth treatment if applied in sequence. For those still unimproved after multiple courses of psychotherapy or medication, 50 percent to 60 percent response rates are still possible with electroconvulsive therapy. Newer treatment alternatives include the herb St. John’s wort, acupuncture, and “phototherapy” with bright white lights. There is fairly good evidence that the winter form of seasonal depression responds to phototherapy about as well as to conventional treatments, but the treatment can be time-consuming: up to two hours a day in front of a 10,000-lux light box. St. John’s wort is a relatively inexpensive (about $15 per month) and usually well tolerated nonprescription remedy that is quite popular in Germany. Despite some evidence of effectiveness, however, its value compared with newer treatments has not been proven. Taking it without a physician’s oversight poses some concerns, such as the danger of drug interactions. For example, St. John’s wort speeds metabolism of certain medications, including birth control pills and some of the antiviral medications used to treat AIDs, which may lessen their effectiveness. Interest in the potential of acupuncture for depression has only recently surfaced in the West. It is too early to determine whether it is as effective as other treatments. With all that is now known about depression, well over half of people who suffer from it will experience relief after medical treatment. Research now under way aims to produce both better treatments and better ways of matching people with particular treatments to yield faster and more lasting responses.

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